Human fibrosarcoma cell lines have been found to be transformed in vitro and tumorigenic when injected into immunosuppressed animals. We have hybridized one human fibrosarcoma cell line (HT-1080) with mouse peritoneal macrophages and with contact-inhibited mouse fibroblasts. Three different types of somatic cell hybrids were obtained: (1)\those which have lost mouse chromosomes; (2)\those which have retained the entire complement of mouse and human chromosomes; and (3)\those which have lost human chromosomes. These different hybrid cells were found to be tumorigenic in nude mice. We propose: (1)\to identify the human chromosome responsible for the expression of malignancy in the HT-1080 human fibrosarcoma cell line; (2)\to characterize the tumor antigens expressed in the cell surface of the HT-1080 human fibrosarcoma cells; (3)\to identify the human chromosome responsible for the expression of malignancy in additional human fibrosarcoma cell lines; and (4)\to clone the gene(s) responsible for malignancy.